Passive immunization with broadly neutralizing antibodies is a promising approach for prevention and treatment of HIV-1 infection. We have generated an HIV-1 neutralizing human antibody which binds to the principal neutralizing determinant (PND) of the envelope glycoprotein gp12O. The antibody shows strong binding to diverse laboratory isolates as well as good neutralization ability for some of these isolates. Like other mAbs of this class, our antibody is limited in binding to a few HIV-l subtypes. We propose in this Phase I study to broaden the reactivity of the antibody through a novel combination of molecular modelling and use of the antibody phage display system. In a phase II study, promising clones with increased reactivity will be analyzed in more detail for biological activity. This analysis will also lead to further refinement of our approach.